Seizures (generalised or partial) occur most often in 10 to 15% of patients with palliative care needs due to primary or secondary brain tumours, cerebrovascular disease, epilepsy or biochemical abnormalities, for example low sodium, hypercalcaemia or uraemia. 70% of patients with brain tumours have seizures during the course of their illness. An advance care plan is particularly important for people at risk of seizures and may help to avoid unnecessary hospital admission.

• Eliminate other causes of loss of consciousness or abnormal limb or facial movement, for example vasovagal episode, postural hypotension, arrhythmia, hypoglycaemia, extrapyramidal side effects from dopamine antagonists.
• Find out if the patient has had previous seizures or is at risk. Exclude history of epilepsy, previous secondary seizure, known cerebral disease and dementia.
• Ensure there are no problems with usual anti-epileptic drug therapy – check patient is able to take oral medication. Drug interactions are common (for example corticosteroids reduce the effect of carbamazepine and phenytoin). Please check the British National Formulary (BNF).

The management advice below is intended for situations where the standard medical protocols are unavailable or not assessed to be in the patient’s best interest.   

• Choice of anti-epileptic drug is guided by seizure type, potential for drug interactions and co-morbidities. Consider discussion with epilepsy specialist when identifying seizure type and management plan for patient. The adverse effects and interactions profiles of these medications should be key in deciding management of individuals. Levetiracetam is better tolerated in patients aged 60 years and over.
• Dying patients unable to take oral medication: anti-epileptic drugs have a long half-life, however ongoing management should be considered:
• †Midazolam 5mg subcutaneously (SC). Buccal midazolam is another option and can be acceptable for patients. 
• †Midazolam 20mg to 30mg via continuous subcutaneous infusion (CSCI) over 24 hours can be used as maintenance therapy.
• †Subcutaneous levetiracetam via CSCI over 24 hours is an option to be considered. Conversion of oral to CSCI of levetiracetam is 1:1.

 Seizure management in patients unsuitable for standard medical management

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• Midazolam injection is licensed for intravenous (IV), intramuscular (IM) and rectal use but it can also be given (unlicensed) via SC, CSCI, intranasal and buccal routes. There are newer buccal preparations available and these may be easier and maintain more dignity for the patient than rectal diazepam.
• Although first seizures are not usually treated, for those with intracranial tumours, anti‑epileptic drugs are normally commenced following first seizure. There is no evidence of benefit of prophylactic anti-epileptic drugs (before any seizure occurs). 30% of patients with primary brain tumours have a seizure in the last week of life.
• Consider commencement of (or review dose of) corticosteroid in those with intracranial tumour and seizure.
• Levetiracetam and lamotrigine do not significantly induce enzymes and will have minimal interactions with other medications such as chemotherapy.
• Monitor effect of medication which can lower seizure threshold such as QThaloperidol or levomepromazine; review need and dose if there is definite exacerbation of seizure activity as a result.
• In patients with moderate to severe renal impairment defined by a creatinine clearance of less than 30ml/min/1.73m², consider reducing levetiracetam dose to 250mg twice daily or 500mg/24 hours via syringe pump.
• Seizures are frightening for patients and their families. Educate and address any concerns such as desired management of further seizures, management of risk of seizure recurrence if stopping anti-epileptic drugs, for example due to swallowing difficulties.
• If relevant, it is important to remind patients that anti-epileptic drug treatment would be life-long and that there are implications for driving following seizures.
• Buccolam® (midazolam 5mg/ml) is unlicensed for use in adults. Epistatus® (midazolam 10mg/ml) is unlicensed for use in adults. Check local policy for product choice.

Scottish Palliative Care Guidelines - Levetiracetam (Subcutaneous Infusion). 2018 [cited 2019 February 08]; Available from https://www.palliativecareguidelines.scot.nhs.uk/guidelines/medicine-information-sheets/levetiracetam-(subcutaneous-infusion).aspx

British National Formulary.2017. Available from https://www.medicinescomplete.com/mc/bnf/current/PHP-bnf-interactions-list.htm

BMJ Best Practice. Focal seizures. 2018 [cited 2018 Oct 04]; Available from: https://bestpractice.bmj.com/topics/en-gb/544.

BMJ Best Practice. Generalised seizures. 2018 [cited 2018 Oct 04]; Available from:https://bestpractice.bmj.com/topics/en-gb/543.

Dickman A, Schneider J. The Syringe Driver. 4th ed: Oxford University Press; 2016.

Freiherr von Hornstein W, editor. Levetiracetam continuous subcutaneous infusion in the management of seizures. First experience. Poster presentation IAPC Education & Research Seminar 2014.

Freiherr von Hornstein W, O'Gorman A, Richardson J, Wilson M, Carroll M, editors. Successful Management of Seizures until the End of Life using Levetiracetam Continuous Subcutaneous Infusion. Poster presentation NCRI Cancer Conference Abstracts; 2014.

Kerrigan S, Grant R. Antiepileptic drugs for treating seizures in adults with brain tumours. 2011 [cited 2018 Oct 04]; Available from: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD008586.pub2/epdf/standard.

Lopez-Saca JM, Vaquero J, Larumbe A, Urdiroz J, Centeno C. Repeated use of subcutaneous levetiracetam in a palliative care patient. J Pain Symptom Manage. 2013;45(5):e7-8.

NICE. Epilepsies: diagnosis and management CG137. 2018 [cited 2018 Oct 04]; Available from: https://www.nice.org.uk/guidance/cg137.

Pruitt AA. Medical management of patients with brain tumors. Continuum (Minneap Minn). 2015;21(2 Neuro-oncology):314-31.

Remi C, Lorenzl S, Vyhnalek B, Rastorfer K, Feddersen B. Continuous subcutaneous use of levetiracetam: a retrospective review of tolerability and clinical effects. J Pain Palliat Care Pharmacother. 2014;28(4):371-7.

Royal Pharmaceutical Society. BNF - Levetiracetam. 2018 [cited 2018 Oct 04]; Available from: https://www.medicinescomplete.com/#/content/bnf/_695768521.

SIGN. Diagnosis and management of epilepsy in adults No143. 2015 [cited 2018 Oct 04]; Available from: https://www.sign.ac.uk/our-guidelines/diagnosis-and-management-of-epilepsy-in-adults/.

Twycross R, Wilcock A, Howard P. Palliative Care Formulary PCF6. 6th ed. England: Pharmaceutical Press; 2017.